Oxidative Stress Induces Dephosphorylation of τ in Rat Brain Primary Neuronal Cultures

• Published in: Journal of neurochemistry 1997-04, Vol.68 (4), p.1590-1597
• Main Authors: Davis, Daniel R., Anderton, Brian H., Brion, Jean‐Pierre, Reynolds, C. Hugh, Hanger, Diane P.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Animals; Biological and medical sciences; Blotting, Western; Cell Compartmentation - physiology; Cells, Cultured - chemistry; Cells, Cultured - metabolism; Cerebral Cortex - cytology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Excitotoxicity; Free radicals; Free Radicals - metabolism; Hydrogen Peroxide - pharmacology; Medical sciences; Microtubule-Associated Proteins - analysis; Microtubule-Associated Proteins - metabolism; Neurodegeneration; Neurology; Neurons - chemistry; Neurons - cytology; Neurons - enzymology; Oxidants - pharmacology; Oxidative Stress - physiology; Phosphoric Monoester Hydrolases - antagonists & inhibitors; Phosphoric Monoester Hydrolases - metabolism; Phosphorylation; Rats; Reactive oxygen species; Reactive Oxygen Species - metabolism; tau Proteins - analysis; tau Proteins - metabolism
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1997.68041590.x

: Oxidative stress and free radical damage have been implicated in the neurodegenerative changes characteristic of several neurodegenerative diseases, including Alzheimer's disease. There is experimental evidence that the neurotoxicity of β‐amyloid is mediated via free radicals, and as the deposition of β‐amyloid apparently precedes the formation of paired helical filaments (PHF) in Alzheimer's disease, we have investigated whether subjecting primary neuronal cultures to oxidative stress induces changes in the phosphorylation state of the principal PHF protein τ that resemble those found in PHF‐τ. Contrary to causing an increase in τ phosphorylation, treatment of neurones with hydrogen peroxide caused a dephosphorylation of τ and so we conclude that oxidative stress is not the direct cause of τ hyperphosphorylation and hence of PHF formation.